Identification of cytogenetic subclasses and recurring chromosomal aberrations in AML and MDS with complex karyotypes using M-FISH

Complex chromosomal aberrations (CCAs) can be detected in a substantial pro portion of AML and MDS patients, de novo as well as secondary or therapy-re lated, and are associated with an adverse prognosis. Comprehensive analysis of the chromosomal rearrangements in these complex karyotypes has been ham pered by the limitations of conventional cytogenetics. As a result, our kno wledge concerning the cytogenetics of these malignancies is sparse. Here we describe a multiplex-FISH (M-FISH) study of CCAs in 36 patients with AML a nd MDS. IM-FISH generated a genome-wide analysis of chromosomal aberrations in CCAs, establishing several cytogenetic subgroups. -5/5q- was demonstrat ed in the majority of patients (86%). Other rearrangements (present with or without -5/5q-) included; deletion of 7q (47%), 3q rearrangements (19%), a nd MLL copy gain or amplification (17%). These genetic subgroups seem to di splay biological heterogeneity; MLL copy gain or amplification in associati on with 5q- was detected only in AML patients and was significantly associa ted with extremely short survival (median overall survival; 30 days, P = 0. 0102). A partially cryptic t(4;5)(q31;q31), a balanced t(1;8)(p31;q22), and an unbalanced der(7)t(7;14)(q21;q13) were detected as possible new recurre nt rearrangements in association with CCAs. Novel reciprocal translocations included t(5;11)(q33;p15)del(5)(q13q31) and t(3;6)(q26;q25). We conclude t hat AML and MDS with CCAs can be subdivided into molecular cytogenetic Subc lasses, which could reflect different clinical behavior and prognosis, and that three recurrent chromosomal aberrations are associated with karyotype complexity. (C) 2002 Wiley-Liss, Inc.